Long non-coding RNA Linc00525 as a prognostic factor to regulate proliferation and apoptosis in colorectal cancer.

Abstract

e15085 Background: Colorectal cancer (CRC) is one of the most common digestive system tumors and poses a serious threat to human health. More and more studies have shown that long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of various tumors. They regulate a variety of cancer biology, such as proliferation, apoptosis, invasion and metastasis. Abnormally expressed lncRNAs are closely related to colorectal cancer. The purpose of this study was to find lncRNAs associated with the development of colorectal cancer and to explore its function and mechanism. Methods: (1) By analyzing the expression profile of lncRNAs in colorectal cancer-normal tissues in GEO databases, the abnormal expression of lncRNA LINC00525 was screened. Colorectal cancer tissues, adjacent normal colon tissues and colorectal cancer cell lines (HCT116, DLD1, HT-29, SW480) were detected by qRT-PCR. We analyzed the relationship between expression of LINC00525 and clinical features. (2) The biological functions of LINC00525 in HCT116, DLD1 and SW480 were peformed in vitro by MTT, clone formation assay, EDU and flow cytometry. (3) The effect of LINC00525 on tumorigenesis in vivo was evaluated by nude mice model. (4) The expression of lncRNA LINC00525 was knocked down in colorectal cancer cell lines (HCT116, SW480), and the mRNA expression levels of P15, P21, P27 and KLF2 were detected by qRT-PCR. Results: (1) Microarray data and qRT-PCR verification showed that the expression of lncRNA LINC00525 in colorectal cancer tissues and colorectal cancer cell lines was significantly upregulated. The overexpression of LINC00525 was positively correlated with clinical stage and tumor size. (2) Knockdown of LINC00525 in colorectal cancer cell lines could inhibit cancer cell proliferation and induce apoptosis. In SW480 and HCT116 cell lines, cells were arrested in G0/G1 phase after knocking down LINC00525. (3) Subcutaneous xenograft experiments in nude mice further confirmed that knockdown of LINC00525 could inhibit the tumor growth. (4) After knocking down the expression of LINC00525 in HCT116 and SW480 cell lines, the expression of mRNAs of tumor suppressor genes P15, P21, P27 and KLF2 increased. Conclusions: Our studies suggested that LINC00525 was significantly upregulated in colorectal cancer tissues. Mechanism studies had shown that LINC00525 could regulate the expression of KLF2, P15, P21 and P27 in CRC cell lines, and then affect cell proliferation and apoptosis.